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New Way to Repair Bone without Adding Cells

University of Michigan Researchers Develop Novel Approach

Ann Arbor, MI — January 14, 2016 — For the first time, scientists at the University of Michigan have developed highly branched biodegradable polymers that self-assemble into a nano-scale “shell-in-shell” structure to efficiently deliver a microRNA. Read more...

These novel microRNA-loaded nano-structures are released in a controlled manner in a three-dimensional scaffold that allows bones to regenerate without adding cells. This key breakthrough is published in the January online issue of Nature Communications. The paper, “Cell-Free 3D Scaffold with Two-Stage Delivery of miRNA-26a to Regenerate Critical Sized Bone Defects,” was written by Xiaojin Zhang, Yan Li, Y. Eugene Chen, Jihua Chen and Peter X. Ma.

“The new technology we have been working on opens doors for new therapies using DNA and RNA in regenerative medicine and boosts the possibility of dealing with other challenging human diseases,” Ma said.

Why the Breakthrough is Important

Tissue loss and organ failures are devastating to patients. Bone defines human body shape and permits motion in addition to protecting delicate organs. Millions of patients worldwide suffer from bone loss and associated functional deficiencies. While orthopaedic and oral-facial surgeons use metallic alloys or harvested bone tissue to treat patients with bone loss, these often have some limitations due to their lack of biological function and possible immune rejection.

Tissue engineers made significant advances in the past two decades in developing biomaterials (scaffolds), identifying stem and progenitor cells, and discovering growth factors to facilitate bone regeneration. However, robustly regenerating high quality bone for a specific application remains elusive with the current technologies.

One of the major challenges in overcoming that obstacle is a need to add cells to facilitate bone regeneration. That’s because living cells have their own “personalities” which depend on many factors such as type, age, gender, or location in the body. Cell isolation methods and external cultures may change the properties of the cells, including their bone-forming ability or possibly even change them into unwanted cells such as tumor cells. As a result of outcomes, cell-based therapies face rigorous regulatory scrutiny and must satisfy demanding experimental trials before they can be used clinically and eventually benefit patients.

What’s Different

The Ma lab takes a new approach. It has developed technologies that turn on the desired regenerative capacity of a patient’s cells rather than using externally added cells. MicroRNAs are increasingly recognized as cell regulators but have not been successfully utilized to regenerate tissues. That’s because microRNAs cannot enter cells easily, are unstable in vivo, and are difficult to introduce into desired sites.

The key breakthrough reported in the Nature Communications article includes a novel polymer that can self-assemble into highly stable and efficient vehicles to transport a microRNA into cells. This approach achieves controllable long-term release of the microRNA-loaded vehicle to enter a patient’s cells and to localize the microRNA in the desired three-dimensional space.

Bone repair is especially challenging in patients who have deficient healing capacity such as patients with osteoporosis. Ma’s research team has demonstrated that the new controlled, localized and highly efficient microRNA delivery strategy can regulate multiple bone-forming genes and fully regenerated critical-sized bone defects in osteoporotic mice. The Ma lab is now expanding the studies into large animals and evaluating the technology for potential use in human patients.

Dr. Peter Ma is the Richard H. Kingery Endowed Collegiate Professor of Dentistry and a professor of Biomedical Engineering, Macromolecular Science and Engineering, and Materials Science and Engineering at the College of Engineering.